O型口蹄疫病毒蛋白酶编码序列及氨基酸序列变化的分析

Analysis on the alterations of the viral protease-coding sequence and the amino acid sequence in O type of foot and mouth disease virus

目的与方法从GenBank中下载了19株O型口蹄疫病毒的Lab、3C、3D基因,结合本实验室收录的FMDVOA/58Lab、3C、3D的序列信息,分析比较了三种FMDV蛋白酶(Lpro,3Cpro,3Dpol)的编码序列和氨基酸序列。结果这FMDV具有的蛋白酶的编码序列在突变上没有显著差异(P>0.05),而在氨基酸序列的突变上存在着显著差异(P<0.01)。通过多重比较发现Lpro与3Cpro和3Dpol在氨基酸突变上存在差异(P<0.05),而3Cpro和3Dpol之间突变差异不显著。结论利用Swiss-pdbViewer蛋白质分析软件模拟三种蛋白酶中各个突变热点氨基酸残基的替换,发现突变热点不影响三种蛋白酶的空间结构。这表明病毒基因组在复制过程中的突变只是FMDV变异的原始动力,而FMDV变异的方向性进化动力是感染FMDV的宿主细胞对病毒蛋白酶功能造成的选择压力。

Three encoding sequence genes （Lab, 3C, 3D） from 19 isolates of O-serotype of foot and mouth disease virus （FMDV） were down-loaded from GenBank. And the coding and amino acid sequences of 3 FMDV proteases （L^pro,3C^pro,3D^pol） were compared with the FMDV OA/58 serotype Lab, 3C, 3D sequences abstracted in our laboratory and qualified by va- riance analysis and multiple analysis（Duncan method）. The experimental results revealed that the Lab, 3C and 3D genes had similar nucleotide mutation rates（P〉0.05）. However, overall analysis of the amino acid substitutions revealed that the L^pro- coding region was more prone to amino acid alterations than 3C^pro and 3D^pol- coding regions（P〈0.01）, hut via multiple compar ison, at the amino acid mutation, both 3C^pro and 3D^pol showed no significant difference. Depending on Swiss-pdb-Viewer sole to simulate amino acid alterations at mutation hotspots, the findings showed that these alterations at hotspots failed to ruin the spatial structures of these 3 proteases. This result presents that the nueleotide mutation just acts on dynamics related to FMDV mutation, but the real evolutionary power must depend on the infected host cells to select functions with each viral proteases.